CTLA4 Autoimmunity-Associated Genotype Contributes to Severe Pulmonary Tuberculosis in an African Population

The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (P_{corrected [cor]} = 0.002, P_cor = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB.     

Glucoraphasatin: Chemistry, occurrence, and biological properties

Glucoraphasatin is an atypical glucosinolate mainly found in Raphanus sativus roots and sprouts. This review focuses on the chemistry, the occurrence, and the biological properties of glucoraphasatin.     

In situ nick translation of metaphase chromosomes with biotin-labeled d-UTP

Summary Conditioned culture medium from Daudi cells was used as a source of soluble H-Y antigen. Concentrated culture medium was labeled with ¹²⁵I and then fractionated by gel filtration. Column fractions were assayed for the presence of H-Y antigen by urease-ELISA. H-Y antigen-containing fractions were then pooled and subjected to an improved immunoprecipitation protocol. Three predominant H-Y antigenic proteins were identified with estimated molecular weights of above 200,000, 50,000, and 20,000.     

UDP-N-acetylglucosamine 1-carboxyvinyl-transferase from Acinetobacter calcoaceticus

Abstract We have analyzed the sequence downstream of rpoN from Zcinetobacter calcoaceticus and identified an open reading frame encoding a protein with high similarity to UDP- N -acetylgucosamine 1-carboxyvinyl-transferase (MurZ). Multicopy plasmids encoding this enzyme conferred phosphomycin resistance to A. calcoaceticus . The polar effect of a rpoN mutation on the phosphomycin resistance level suggests that murZ is, in part, cotranscribed with rpoN . These observations confirm that A. calcoaceticus represents the first exceptin from a conserved genetic context of rpoN observed in several other Gram-negative bacteria.     

A High-Content Small Molecule Screen Identifies Sensitivity of Glioblastoma Stem Cells to Inhibition of Polo-Like Kinase 1

Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF^−/−, or p53^−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value.     

Changes in responsiveness to ethylene and gibberellin during corolla expansion ofIpomoea nil

Corolla expansion inIpomoea nil appears to be triggered by changes in gibberellin concentration and ethylene production during development. We investigated the role of responsiveness to GA and ethylene in corolla expansion. The effects of growth regulators applied in vitro were measured as a change in area of corolla segments from younger (15–17 mm) and older (18–20 mm) whole corollas. Applied gibberellic acid (GA₃) significantly (p < 0.05) promoted growth in the younger segments but was less effective in the older segments. Moreover, applications of the GA biosynthesis inhibitors, PP333 (paclobutrazol) AMO₁₆₁₈ (2-isopropyl-4-dimethylamino-5-methylphenyl-1-piperidinecarboxylate methyl chloride), chlorocholine chloride, and tetcyclasis had little effect on younger segments but inhibited growth of older segments. The older corollas have apparently synthesized and accumulated enough GA-like substances to become less responsive to additional applied GA₃. The amount of growth induced by applied or endogenous GA depended on the amount of ethylene simultaneously produced in the tissue. The younger corollas rapidly produced ethylene from endogenous 1-aminocyclopropane-1-carboxylic acid (ACC) and did not respond to applied ACC whereas the older corollas naturally produced much less ethylene and were significantly (p < 0.05) inhibited by applied ACC. When ethylene production was inhibited by applying aminoethoxyvinylglycine (AVG), growth was promoted in all segments. However, only the growth of the younger segments was further stimulated by simultaneously applied AVG and GA₃ over the GA₃ control. Thus the differential responses of segments from 15- to 20-mm long corollas to applied growth regulators reflect developmental changes in responsiveness of the developing corolla. The change in responsiveness is attributed in part to the changes in production of endogenous growth regulators and to the effect of one endogenous plant growth regulator (PGR) on the responsiveness of the corolla to another PGR.     

Names and naming: Instances from the ORU-IGBO

Conclusion People have many names. But, changing one's name is no small thing. It can signify a major step in life or an embarrassing story, as in the last case.A person has a complex individual identity. His collective identity is clear from the moment he is conceived. He is one with a body of people, his kinsmen, who share one common ancestor and through him access to land and resources. The continuation of this group and its name is perpetuated through paternal descent.Kingroup membership ensures a person's place in life, his right to exist, eat, live and enjoy. But, who is he, apart from being a kinsman? Which kinsman is he? How are people going to interact with him? His individual identity will become clear through time. He is a re-incarnation of ancestor x. The circumstances of his birth were such. He behaves like this. He has these personal traits. This has happened to him. He has achieved that. There is no permanent role attached to an individual. He is neither bound to class nor caste. He is dynamic and changes constantly. His life is one of achievement, constant striving and upward mobility till death — when it all begins again. His name signals his state of being in time and existence.Sabine Jell-Bahlsen is an anthropologist and filmmaker.     

Fanconi's anaemia: correlation of genetic complementation group with psoralen/UVA response

Summary The correlation found by Moustacchi (1987) between cellular response to a crosslinking challenge and genetic heterogeneity in Fanconi's anaemia is confirmed for an earlier set of complementation groups (Zakrzewski and Sperling 1980). This allows the matching of the two independently established complementation groupings and better characterization of their DNA repair-related biochemical properties.